Antibodies to Variant Surface Antigens of Plasmodium falciparum–Infected Erythrocytes Are Associated with Protection from Treatment Failure and the Development of Anemia in Pregnancy
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BACKGROUND: In pregnancy-associated malaria (PAM), Plasmodium falciparum-infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonize IEs for phagocytic clearance, helping to prevent maternal anemia and low birth weight in infants. METHODS: Using serum samples from 141 pregnant Malawian women with parasitemia enrolled in a randomized trial of antimalarials and VSA-PAM-expressing CS2 IEs, we quantified levels of immunoglobulin (Ig) G to VSA-PAM by flow cytometry and levels of opsonizing antibodies by measuring uptake of IEs by THP1 promonocytes. RESULTS: After controlling for gravidity and antimalarial treatment, higher levels of IgG to VSA-PAM were associated with decreased anemia at delivery (odds ratio [OR], 0.66 [95% confidence interval {CI}, 0.46-0.93]; P = .018) and were weakly associated with decreased parasitological failure (OR, 0.78 [95% CI, 0.60-1.03]; P = .075), especially reinfection (OR, 0.73 [95% CI, 0.53-1.01]; P = .057). Higher levels of opsonizing antibodies to CS2 IEs were associated with less maternal anemia (OR, 0.31 [95% CI, 0.13-0.74]; P = .008) and treatment failure (OR, 0.48 [95% CI, 0.25-0.90]; P = .023), primarily because of recrudescent infection (OR, 0.49 [95% CI, 0.21-1.12]; P = .089). CONCLUSION: Higher levels of both IgG antibodies to VSA-PAM and opsonizing antibodies, a functional measure of immunity, correlate with parasite clearance and less anemia in pregnancy malaria.
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Antibodies that blocked adhesion of infected erythrocytes to chondroitin sulfate A were associated with reduced risk of anemia in women exposed to SMIs during pregnancy, suggesting a role for these antibodies in opsonization of infected erythrocytes.
“Antibodies that blocked adhesion of IEs to CSA were associated with reduced risk of anemia in women exposed to SMIs during pregnancy, suggesting a role for these antibodies in opsonization of IEs (35).”
From Clinical outcomes of submicroscopic infections and correlates of protection of VAR2CSA antibodies in a longitudinal study of pregnant women in Colombia (2018) · cites this paper as [35]
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Self-citation
- Authors
- Feng, G., Aitken, E., Yosaatmadja, F., Kalilani, L., Meshnick, S. R., Jaworowski, A., Simpson, J. A., & Rogerson, S. J.
- Affiliations
- The Royal Melbourne Hospital (AU)
- University of Malawi (MW)
- University of North Carolina at Chapel Hill (US)
- Burnet Institute (AU)
- The University of Melbourne (AU)
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07-15
- Volume
- 200
- Issue
- 2
- Pages
- 299-306
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC2759893
- OpenAlex
- W2144696623
- Cited by
- 69
- References
- 41
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 10 · 2014: 9 · 2013: 6 · 2012: 5
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI049084)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- malaria in pregnancy, Plasmodium falciparum, variant surface antigens, opsonic antibodies, IgG, anemia in pregnancy, treatment failure, reinfection, recrudescent infection, placental sequestration, parasite clearance, placental adhesions
- MeSH terms
- Adolescent, Adult, Anemia, Animals, Antibodies, Protozoan, Antigens, Protozoan, Antigens, Surface, Antimalarials, Erythrocytes, Female, Flow Cytometry, Humans, Immunoglobulin G, Malawi, Membrane Glycoproteins, Plasmodium falciparum, Pregnancy, Pregnancy Complications, Parasitic, Malaria, Falciparum, Young Adult
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